Prognosis and Immune Infiltration Analysis of m6A RNA methylation regulators in Skin cutaneous melanoma and differential analysis with cuproptosis

Abstract Background Skin cutaneous melanoma (SKCM) is the most malignant tumor among skin cancers. We aimed to identify the role of m6A regulated genes in the prognosis and tumor immune microenvironment of SKCM. We further elevated the expression level of cuproptosis-related genes in different risk groups. Methods The transcriptome data of 471 SKCM tissues from the XENA database and 812 normal samples from GTEx were obtained.The univariate Cox regression analysis was used to explore the relationship of m6A related genes and the clinical outcomes of SKCM The least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a risk model for m6A regulated genes. Furthermore, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. Also, the immune cell infiltration was analyzed using CIBERSORT. In addition, we assessed the expression level of cuproptosis-related genes in SKCM samples and its role in different risk sets. Expression validation of cuproptosis-associated genes in YTHDF3 downregulated melanoma cell lines by RT-qPCR. Results In this study, we found that m6A-related genes were differentially expressed in melanoma and normal samples. Eight of them were significantly related to prognosis. The risk model based on HNRNPA2B1, METTL3, WTAP, METTL15, YTHDC1 and RBMX was constructed and validated. Besides, the biological processes and signaling pathway were analyzed by GO and KEGG analysis. Moreover, the infiltration of immune cells in different risk sets were explored and we discovered the infiltration level of CD8 + T cells, T cell CD4 + memory activated, NK cell activated and Macrophage M1 was negatively correlated with risk score. We further detected the expression level of ten cuproptosis-related gens in different risk groups. Among them, the MTF1, PDHB and FDX1 were differentially expressed and the lower expression appeared to correlate with higher risk score. Finally, we found that the expression of MTF1 and PDHB was increased when m6A regulator YTHDF3 was downregulated. Conclusion Our study demonstrated the prognostic value of m6A-related genes in SKCM and their role in tumor immune microenvironment. In addition, we creatively explored the relationship between m6A RNA methylation regulators and cuproptosis-related genes in SKCM.